DRUG TRANSPORT/METABOLISM IN PREGNANCY

妊娠期药物转运/代谢

• 批准号: 7603437
• 负责人: MARY F HEBERT
• 金额: $ 0.11万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603437
• 关键词: Antiviral Agents; Blood; Clinical Data; Computer Retrieval of Information on Scientific Projects Database; Digoxin; Dose; Drug Exposure; Drug Kinetics; Drug Transport; Drug usage; Enzymes; Fetus; Funding; Grant; Infection; Institution; Metabolism; Midazolam; Oral; P-Glycoprotein; P-Glycoproteins; Pharmaceutical Preparations; Postpartum Period; Pregnancy; Pregnancy Trimesters; Pregnant Women; Recruitment Activity; Research; Research Personnel; Resources; Sampling; Source; United States National Institutes of Health; Urine; Vulnerable Populations; Week; Woman; cytochrome P450 3A; day; design; men

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Drugs are administered to pregnant women, and therefore their fetuses without the necessary clinical data in these vulnerable populations. To determine the correct dose of a drug to administer during pregnancy, it is important to know if the pharmacokinetics of the drug are different in pregnant women when compared with men or non-pregnant women. Many drugs administered in pregnancy are substrates of P-glycoprotein (P-gp) or cytochrome P450 3A enzymes (CYP3A4/5) or both. We have evidence that for two of the antiviral drugs used to treat infections there is a 3-6 fold decrease in overall drug exposure at 30 weeks gestation as compared to postpartum. Both of these antiviral drugs are metabolized by CYP3A4/5 and transported by P-gp. This study is designed to evaluate how a woman's body handles digoxin (a substrate for P-gp) and midazolam (a substrate for CYP3A4/5) during pregnancy as compared to postpartum. Subjects will receive two oral doses of digoxin (0.25 mg) and two oral doses of midazolam (2 mg). One digoxin study day and one midazolam study day will occur during the 3rd trimester of pregnancy and the other digoxin study day and midazolam study day will occur postpartum. Blood and urine samples will be collected throughout all study days. Healthy pregnant women prior to 28 weeks gestation will be recruited for this study.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 对孕妇及其胎儿施用药物时，没有这些弱势群体必要的临床数据。 为了确定怀孕期间服用药物的正确剂量，重要的是要了解孕妇与男性或非孕妇相比药物的药代动力学是否不同。 妊娠期服用的许多药物都是 P-糖蛋白 (P-gp) 或细胞色素 P450 3A 酶 (CYP3A4/5) 或两者的底物。 我们有证据表明，与产后相比，两种用于治疗感染的抗病毒药物在妊娠 30 周时的总体药物暴露量减少了 3-6 倍。 这两种抗病毒药物均由 CYP3A4/5 代谢并由 P-gp 转运。 本研究旨在评估怀孕期间与产后相比，女性身体如何处理地高辛（P-gp 的底物）和咪达唑仑（CYP3A4/5 的底物）。 受试者将接受两次口服剂量的地高辛（0.25 毫克）和两次口服剂量的咪达唑仑（2 毫克）。 一个地高辛研究日和一个咪达唑仑研究日将在妊娠第三个月期间进行，另一地高辛研究日和咪达唑仑研究日将在产后进行。 将在所有研究日收集血液和尿液样本。 本研究将招募妊娠 28 周之前的健康孕妇。